The Copy Number Variation (CNV) Project

Genetic diseases are caused by mutations in DNA sequences. The Copy Number Variation (CNV) Project investigates the impact on human health of CNVs - gains and losses of large chunks of DNA sequence consisting of between ten thousand and five million letters. We already know that many inherited genetic diseases result from structural mutations or CNVs; we also know that there are Copy Number Variants that protect against HIV infection and malaria. The contribution of CNV to the common, complex diseases, such as diabetes and heart disease, is currently less well understood.

[Matt Hurles, Genome Research Limited]

More pages on the CNV project:


Genetic mutations of any type that increase the chance of an individual developing a common disease are also likely to be found at reasonable frequencies in apparently healthy populations. A range of promising new technologies should, for the first time, allow us to scan the entire human genome for CNV in a single experiment. We are comparing these new technologies for screening hundreds of apparently healthy individuals for CNV.

Using these technologies we are characterising functionally-relevant CNVs at as high resolution as possible, incorporating these variants within association studies for complex diseases, and developing a public resource to facilitate integration of CNV within medical genetic studies.

The copy number variation project draws upon expertise present in several different groups at the Sanger Institute, including: new sequencing technologies, microarray-based analyses, cytogenetics, population genetics, comparative genomics and bioinformatics.

In addition, we have established an international consortium to enable us to achieve our objectives. Together with Charles Lee (Harvard Medical School) and Steve Scherer (Hospital for Sick Kids, Toronto) we are working closely with the developers of leading edge commercial platforms to optimise technologies capable of revealing copy number variation at the highest resolution.

The questions that drive our research are:

  • How much copy number variation (CNV) exists between human genomes?
  • How best can CNVs be incorporated into whole genome association studies?
  • What is the contribution of copy number variation to genetic disease?
  • What is the relative contribution of different mutational mechanisms to CNV?
  • What is the genomic impact of CNV on gene expression?
  • What role has copy number variation played in recent human evolution?


  • For enquiries about the CNV project, please email
  • Project data and data release - For questions about project data and data release, please contact Nigel Carter or Matt Hurles


  • Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls.

    Wellcome Trust Case Control Consortium, Craddock N, Hurles ME, Cardin N, Pearson RD, Plagnol V, Robson S, Vukcevic D, Barnes C, Conrad DF, Giannoulatou E, Holmes C, Marchini JL, Stirrups K, Tobin MD, Wain LV, Yau C, Aerts J, Ahmad T, Andrews TD, Arbury H, Attwood A, Auton A, Ball SG, Balmforth AJ, Barrett JC, Barroso I, Barton A, Bennett AJ, Bhaskar S, Blaszczyk K, Bowes J, Brand OJ, Braund PS, Bredin F, Breen G, Brown MJ, Bruce IN, Bull J, Burren OS, Burton J, Byrnes J, Caesar S, Clee CM, Coffey AJ, Connell JM, Cooper JD, Dominiczak AF, Downes K, Drummond HE, Dudakia D, Dunham A, Ebbs B, Eccles D, Edkins S, Edwards C, Elliot A, Emery P, Evans DM, Evans G, Eyre S, Farmer A, Ferrier IN, Feuk L, Fitzgerald T, Flynn E, Forbes A, Forty L, Franklyn JA, Freathy RM, Gibbs P, Gilbert P, Gokumen O, Gordon-Smith K, Gray E, Green E, Groves CJ, Grozeva D, Gwilliam R, Hall A, Hammond N, Hardy M, Harrison P, Hassanali N, Hebaishi H, Hines S, Hinks A, Hitman GA, Hocking L, Howard E, Howard P, Howson JM, Hughes D, Hunt S, Isaacs JD, Jain M, Jewell DP, Johnson T, Jolley JD, Jones IR, Jones LA, Kirov G, Langford CF, Lango-Allen H, Lathrop GM, Lee J, Lee KL, Lees C, Lewis K, Lindgren CM, Maisuria-Armer M, Maller J, Mansfield J, Martin P, Massey DC, McArdle WL, McGuffin P, McLay KE, Mentzer A, Mimmack ML, Morgan AE, Morris AP, Mowat C, Myers S, Newman W, Nimmo ER, O'Donovan MC, Onipinla A, Onyiah I, Ovington NR, Owen MJ, Palin K, Parnell K, Pernet D, Perry JR, Phillips A, Pinto D, Prescott NJ, Prokopenko I, Quail MA, Rafelt S, Rayner NW, Redon R, Reid DM, Renwick, Ring SM, Robertson N, Russell E, St Clair D, Sambrook JG, Sanderson JD, Schuilenburg H, Scott CE, Scott R, Seal S, Shaw-Hawkins S, Shields BM, Simmonds MJ, Smyth DJ, Somaskantharajah E, Spanova K, Steer S, Stephens J, Stevens HE, Stone MA, Su Z, Symmons DP, Thompson JR, Thomson W, Travers ME, Turnbull C, Valsesia A, Walker M, Walker NM, Wallace C, Warren-Perry M, Watkins NA, Webster J, Weedon MN, Wilson AG, Woodburn M, Wordsworth BP, Young AH, Zeggini E, Carter NP, Frayling TM, Lee C, McVean G, Munroe PB, Palotie A, Sawcer SJ, Scherer SW, Strachan DP, Tyler-Smith C, Brown MA, Burton PR, Caulfield MJ, Compston A, Farrall M, Gough SC, Hall AS, Hattersley AT, Hill AV, Mathew CG, Pembrey M, Satsangi J, Stratton MR, Worthington J, Deloukas P, Duncanson A, Kwiatkowski DP, McCarthy MI, Ouwehand W, Parkes M, Rahman N, Todd JA, Samani NJ and Donnelly P

    Nature 2010;464;7289;713-20

  • Origins and functional impact of copy number variation in the human genome.

    Conrad DF, Pinto D, Redon R, Feuk L, Gokcumen O, Zhang Y, Aerts J, Andrews TD, Barnes C, Campbell P, Fitzgerald T, Hu M, Ihm CH, Kristiansson K, Macarthur DG, Macdonald JR, Onyiah I, Pang AW, Robson S, Stirrups K, Valsesia A, Walter K, Wei J, Wellcome Trust Case Control Consortium, Tyler-Smith C, Carter NP, Lee C, Scherer SW and Hurles ME

    Nature 2010;464;7289;704-12

  • Large, rare chromosomal deletions associated with severe early-onset obesity.

    Bochukova EG, Huang N, Keogh J, Henning E, Purmann C, Blaszczyk K, Saeed S, Hamilton-Shield J, Clayton-Smith J, O'Rahilly S, Hurles ME and Farooqi IS

    Nature 2010;463;7281;666-70

  • Copy number variation and evolution in humans and chimpanzees.

    Perry GH, Yang F, Marques-Bonet T, Murphy C, Fitzgerald T, Lee AS, Hyland C, Stone AC, Hurles ME, Tyler-Smith C, Eichler EE, Carter NP, Lee C and Redon R

    Genome research 2008;18;11;1698-710

  • A robust statistical method for case-control association testing with copy number variation.

    Barnes C, Plagnol V, Fitzgerald T, Redon R, Marchini J, Clayton D and Hurles ME

    Nature genetics 2008;40;10;1245-52

  • Adaptive evolution of UGT2B17 copy-number variation.

    Xue Y, Sun D, Daly A, Yang F, Zhou X, Zhao M, Huang N, Zerjal T, Lee C, Carter NP, Hurles ME and Tyler-Smith C

    American journal of human genetics 2008;83;3;337-46

  • Diet and the evolution of human amylase gene copy number variation.

    Perry GH, Dominy NJ, Claw KG, Lee AS, Fiegler H, Redon R, Werner J, Villanea FA, Mountain JL, Misra R, Carter NP, Lee C and Stone AC

    Nature genetics 2007;39;10;1256-60

  • Relative impact of nucleotide and copy number variation on gene expression phenotypes.

    Stranger BE, Forrest MS, Dunning M, Ingle CE, Beazley C, Thorne N, Redon R, Bird CP, de Grassi A, Lee C, Tyler-Smith C, Carter N, Scherer SW, Tavaré S, Deloukas P, Hurles ME and Dermitzakis ET

    Science (New York, N.Y.) 2007;315;5813;848-53

  • Breaking the waves: improved detection of copy number variation from microarray-based comparative genomic hybridization.

    Marioni JC, Thorne NP, Valsesia A, Fitzgerald T, Redon R, Fiegler H, Andrews TD, Stranger BE, Lynch AG, Dermitzakis ET, Carter NP, Tavaré S and Hurles ME

    Genome biology 2007;8;10;R228

  • Accurate and reliable high-throughput detection of copy number variation in the human genome.

    Fiegler H, Redon R, Andrews D, Scott C, Andrews R, Carder C, Clark R, Dovey O, Ellis P, Feuk L, French L, Hunt P, Kalaitzopoulos D, Larkin J, Montgomery L, Perry GH, Plumb BW, Porter K, Rigby RE, Rigler D, Valsesia A, Langford C, Humphray SJ, Scherer SW, Lee C, Hurles ME and Carter NP

    Genome research 2006;16;12;1566-74

  • Genome assembly comparison identifies structural variants in the human genome.

    Khaja R, Zhang J, MacDonald JR, He Y, Joseph-George AM, Wei J, Rafiq MA, Qian C, Shago M, Pantano L, Aburatani H, Jones K, Redon R, Hurles M, Armengol L, Estivill X, Mural RJ, Lee C, Scherer SW and Feuk L

    Nature genetics 2006;38;12;1413-8

  • Genome-wide detection of human copy number variations using high-density DNA oligonucleotide arrays.

    Komura D, Shen F, Ishikawa S, Fitch KR, Chen W, Zhang J, Liu G, Ihara S, Nakamura H, Hurles ME, Lee C, Scherer SW, Jones KW, Shapero MH, Huang J and Aburatani H

    Genome research 2006;16;12;1575-84

  • Global variation in copy number in the human genome.

    Redon R, Ishikawa S, Fitch KR, Feuk L, Perry GH, Andrews TD, Fiegler H, Shapero MH, Carson AR, Chen W, Cho EK, Dallaire S, Freeman JL, González JR, Gratacòs M, Huang J, Kalaitzopoulos D, Komura D, MacDonald JR, Marshall CR, Mei R, Montgomery L, Nishimura K, Okamura K, Shen F, Somerville MJ, Tchinda J, Valsesia A, Woodwark C, Yang F, Zhang J, Zerjal T, Zhang J, Armengol L, Conrad DF, Estivill X, Tyler-Smith C, Carter NP, Aburatani H, Lee C, Jones KW, Scherer SW and Hurles ME

    Nature 2006;444;7118;444-54

  • A high-resolution survey of deletion polymorphism in the human genome.

    Conrad DF, Andrews TD, Carter NP, Hurles ME and Pritchard JK

    Nature genetics 2006;38;1;75-81

  • How homologous recombination generates a mutable genome.

    Hurles M

    Human genomics 2005;2;3;179-86

  • Detection of large-scale variation in the human genome.

    Iafrate AJ, Feuk L, Rivera MN, Listewnik ML, Donahoe PK, Qi Y, Scherer SW and Lee C

    Nature genetics 2004;36;9;949-51

  • Microarray based comparative genomic hybridisation (array-CGH) detects submicroscopic chromosomal deletions and duplications in patients with learning disability/mental retardation and dysmorphic features.

    Shaw-Smith C, Redon R, Rickman L, Rio M, Willatt L, Fiegler H, Firth H, Sanlaville D, Winter R, Colleaux L, Bobrow M and Carter NP

    Journal of medical genetics 2004;41;4;241-8

  • Origins of chromosomal rearrangement hotspots in the human genome: evidence from the AZFa deletion hotspots.

    Hurles ME, Willey D, Matthews L and Hussain SS

    Genome biology 2004;5;8;R55

CNV project pages


  • CNVFinder - an algorithm designed to detect copy number variants (CNVs) in the human population from large-insert clone DNA microarray
  • CNVTools - a collection of packages useful in the analysis of copy number variants (CNV).
* quick link -